A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]Subasumstat in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Cumulative Percentage of Urinary Recovery
研究概览
简要总结
The main aim of this study is to assess how the human body of adults with advanced or metastatic solid tumors absorbs, distributes, metabolizes and excretes subasumstat following a single 1 hour infusion of subasumstat.
The study consists of two parts. In Part A, participants will receive a single infusion of C14 radiolabeled subasumstat. In Part B, participants will receive subasumstat treatment for up to 1 year.
详细描述
The drug being tested in this study is called [14C]subasumstat. [14C]Subasumstat is being tested to assess mass balance and absorption, distribution, metabolism, excretion (ADME) of people who have advanced or metastatic solid tumors.
The study will enroll approximately 10 patients. Participants will be enrolled to receive a single dose of [14C]subasumstat:
- [14C]Subasumstat 90 mg
Participants will be administered with a single dose of [14C]subasumstat 90 mg as a 1-hour intravenous (IV) infusion on Day 1 of Part A. All participants will be monitored for up to 14 days postdose. Participants will then have an option to enter Part B of the study to receive non-radiolabelled subasumstat 90 mg, IV infusion on Days 1, 4, 8, and 11 of a 21-day cycle for 3 cycles up to maximum treatment duration of 1 year.
This multi-center trial will be conducted in Hungary. The overall study duration is 12 months for Part A and 24 months for Part B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants have histologically or cytologically confirmed advanced (locally regionally recurrent not amenable to curative therapy) or metastatic solid tumors with no standard therapeutic option with a proven clinical benefit, are intolerant or have refused them.
- •Participants have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
- •Participants demonstrate adequate organ function.
- •Participants have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela.
排除标准
- •Participants received treatment with radioisotopes within 5 half-lives before the first dose of the study drug.
- •Participants received radiolabelled substances, were exposed to radiation sources within 12 months of the first dose in this study, or is likely to receive radiation exposure or radioisotopes within 12 months of the first dose in this study such that participation in this study would increase their total exposure beyond the recommended safe levels.
- •Participants received extended field radiotherapy ≤4 weeks before the start of treatment.
- •Participants have uncontrolled brain metastasis. Participants with treated brain metastases are allowed provided they are radiologically stable, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study treatment.
- •Participants had a second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the patient is not on active anticancer therapies.
- •Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery.
- •Baseline prolongation of the QT interval when corrected using Fridericia's formula (QTcF).
- •Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P450 (CYP) 3A4/5 and strong P-glycoprotein (Pgp) inhibitors.
- •Has active noninfectious pneumonitis or interstitial lung disease that required steroids.
- •History of allogeneic tissue or solid organ transplant.
- •Participants have active bacterial infection requiring systemic therapy <14 days before the start of treatment.
- •Participants have an active HIV or any other relevant congenital or acquired immunodeficiency.
- •Active hepatitis B, or hepatitis C infection.
- •Any of the following uncontrolled heart diseases: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias >Grade 2, pulmonary embolism or symptomatic cerebrovascular events, or any other serious cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
研究组 & 干预措施
Part A: [14C] Subasumstat
Participants received a single dose of [14C] subasumstat 90 milligrams (mg), intravenous (IV) infusion on Day 1 in Part A of the study.
干预措施: [14C] Subasumstat (Drug)
Part B: Subasumstat
Participants received subasumstat 90 mg, IV infusion on Days 1, 4, 8, and 11 of a 21 day cycle for 3 cycles after Part A, followed by weekly maintenance dosing in Part B of the study up to maximum treatment duration of 1 year.
干预措施: Subasumstat (Drug)
结局指标
主要结局
Cumulative Percentage of Urinary Recovery
时间窗: Up to 14 days post-dose
Cumulative percentage of \[14C\]-radioactivity excreted in urine up to the last sampling interval.
Cumulative Percentage of Fecal Recovery
时间窗: Up to 14 days post-dose
Cumulative percentage of \[14C\]-radioactivity excreted in feces up to the last sampling interval.
Cumulative Percentage of Combined Recovery
时间窗: Up to 14 days post-dose
Cumulative percentage of \[14C\]-radioactivity excreted in urine, and feces up to the last sampling interval.
Percentage Of Recovered Total Radioactivity (TRA) In Urine
时间窗: Post-dose Day 1: 0-6 hours (hr), 6-12 hr, Day 2: 12-24 hr, Day 3: 24-48 hr, Day 4: 48-72, Day 5: 72-96 hr, Day 6: 96-120 hr, Day 7: 120-144 hr, Day 8: 144-168 hr, Day 9: 168-192 hr, Day 10: 192-216 hr, Day 11: 216-240 hr, Day 12: 240-264 hr
Percentage of recovered TRA in urine for each interval over the entire period of collection were reported.
Percentage Of Recovered Total Radioactivity (TRA) In Feces
时间窗: Post-dose Day 1: 0-6 hours hr, 6-12 hr, Day 2: 12-24 hr, Day 3: 24-48 hr, Day 4: 48-72 hr, Day 5: 72-96 hr, Day 6: 96-120 hr, Day 7: 120-144 hr, Day 8: 144-168 hr, Day 9: 168-192 hr, Day 10: 192-216 hr, Day 11: 216-240 hr
Percentage of recovered TRA in feces for each interval over the entire period of collection were reported.
次要结局
- Cmax: Maximum Observed Plasma Concentration for Subasumstat and TRA in Plasma and Whole Blood(Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr,4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr)
- Number of Participants With Abnormal Electrocardiogram Findings(Up to approximately 8 months)
- Renal Clearance (CLR) for Subasumstat in Urine(Pre-dose and post-dose at 0-6 hours (hr) and 6-12 hr on Day 1, 12-24 hr on Day 2, 24-48 hr on Day 3, 48-72 hr on Day 4, 72-96 hr on Day 5 up to Day 14)
- Tmax: Time of First Occurrence of Cmax for Subasumstat and TRA in Plasma and Whole Blood(Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr,4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr)
- Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)(Up to approximately 8 months)
- Number of Participants With Abnormal Laboratory Values(Up to approximately 8 months)
- Relative Percentage of Circulatory Metabolites in Plasma(Pre-dose and Post-dose Day 1: 0.5 hr, 1 hr, 2 hr, 4 hr, 8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr and Day 8: 168 hr)
- AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Subasumstat and TRA in Plasma and Whole Blood(Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr,4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr)
- Relative Percentage Excretory Metabolites in Urine(Pre-dose and Post-dose Day 1: 0.5 hr, 1 hr, 2 hr, 4 hr, 8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr and Day 8: 168 hr)
- Relative Percentage of Excretory Metabolites in Feces(Pre-dose and Post-dose Day 1: 0.5 hr, 1 hr, 2 hr, 4 hr, 8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr and Day 8: 168 hr)
- Terminal Disposition Phase Half-life (T1/2z) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data(Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr,4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr)
- Clearance (CL) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data(Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr,4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr)
- Volume of Distribution at Steady-state (Vss) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data(Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr,4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr)
- Number of Participants With One or More Serious Adverse Events (SAEs)(Up to approximately 8 months)
- AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data(Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr 4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr)
- Cumulative Amount of Unchanged Subasumstat Excreted Into the Urine (Aeurine)(Pre-dose and post-dose at 0-6 hours (hr) and 6-12 hr on Day 1, 12-24 hr on Day 2, 24-48 hr on Day 3, 48-72 hr on Day 4, 72-96 hr on Day 5 up to Day 14)